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A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation
For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking me...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582516/ https://www.ncbi.nlm.nih.gov/pubmed/33007887 http://dx.doi.org/10.3390/molecules25194485 |
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author | Karpina, Veronika R. Kovalenko, Svitlana S. Kovalenko, Sergiy M. Drushlyak, Oleksandr G. Bunyatyan, Natalya D. Georgiyants, Victoriya A. Ivanov, Vladimir V. Langer, Thierry Maes, Louis |
author_facet | Karpina, Veronika R. Kovalenko, Svitlana S. Kovalenko, Sergiy M. Drushlyak, Oleksandr G. Bunyatyan, Natalya D. Georgiyants, Victoriya A. Ivanov, Vladimir V. Langer, Thierry Maes, Louis |
author_sort | Karpina, Veronika R. |
collection | PubMed |
description | For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC(50) = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs. |
format | Online Article Text |
id | pubmed-7582516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75825162020-10-29 A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation Karpina, Veronika R. Kovalenko, Svitlana S. Kovalenko, Sergiy M. Drushlyak, Oleksandr G. Bunyatyan, Natalya D. Georgiyants, Victoriya A. Ivanov, Vladimir V. Langer, Thierry Maes, Louis Molecules Article For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC(50) = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs. MDPI 2020-09-30 /pmc/articles/PMC7582516/ /pubmed/33007887 http://dx.doi.org/10.3390/molecules25194485 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Karpina, Veronika R. Kovalenko, Svitlana S. Kovalenko, Sergiy M. Drushlyak, Oleksandr G. Bunyatyan, Natalya D. Georgiyants, Victoriya A. Ivanov, Vladimir V. Langer, Thierry Maes, Louis A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation |
title | A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation |
title_full | A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation |
title_fullStr | A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation |
title_full_unstemmed | A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation |
title_short | A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation |
title_sort | novel series of [1,2,4]triazolo[4,3-a]pyridine sulfonamides as potential antimalarial agents: in silico studies, synthesis and in vitro evaluation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582516/ https://www.ncbi.nlm.nih.gov/pubmed/33007887 http://dx.doi.org/10.3390/molecules25194485 |
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